For a number of different classes of compounds, correlations between biological activity and physical properties calculated by semi-empirical molecular orbital methods have been found. For example, the psychotropic activity of tryptamines and phenethylamines, the tranquilizing properties of phenothiazines, the carcinogenic activity of aromatic hydrocarbons, and the activities of antimalarial, analgaesic, and anaesthetic drugs have been found to increase as the computed energies of the higest occupied molecular orbitals (HOMO's) increase. These correlations have led to postulates that charge transfer from the drug to the active site is involve in the biological action of these compounds. It is possible with currently available instrumentation (photoelectron spectroscopy) to directly and accurately measure the ionization potentials of large molecules, and thus to determine whether statistically valid correlations between actual electron-donor ability and biological activity in a series of molecules actually exist. The goal of this research will be to study the photoelectron spectroscopy of several series of biologically active compounds, to develop an empirical set of rules for the prediction of ionization potentials in complex biologically active systems, to determine whether correlations between the experimentally determined HOMO energies of molecules and their activities (measured by others) exist, to prove the source of these correlations with the aid of perturbation theory and, finally, to use the empirically determined estimates of HOMO energies to facilitate drug design.